Ongoing human chromosome end extension revealed by analysis of BioNano and nanopore data

ABSTRACTThe majority of human chromosome ends remain incompletely assembled due to their highly repetitive structure. In this study, we use BioNano data to anchor and extend chromosome ends from two European trios as well as two unrelated Asian genomes. BioNano assembled chromosome ends are structurally divergent from the reference genome, including both missing sequence (10%) and extensions(22%). These extensions are heritable and in some cases divergent between Asian and European samples. Six ninths of the extension sequence in NA12878 can be confirmed and filled by nanopore data. We identify two sequence families in these sequences which have undergone substantial duplication in multiple primate lineages. We show that these sequence families have arisen from progenitor interstitial sequence on the ancestral primate chromosome 7. Comparison of chromosome end sequences from 15 species revealed that chromosome end missing sequence matches the corresponding phylogenetic relationship and revealed a rate of chromosome extension per chromosome of 0.0020 bp per year in average.